Globoid leukodystrophy (Krabbe's Disease) is a sphingolipidosis caused by an inherited deficieny of activity of the enzyme that hydrolyzes galactose from galactosylceramide. It is a fatal disease resulting from neuropathy and degeneration of central nerveous system white matter with accumulation of globoid macrophages. Canin globoid leukodystrophy (GLD) is an authentic model of GLD in children because the enzymatic deficiency and resultant pathology is the same in both species. Our goal is to understand the morphologic and biochemical events that constitute the disease process in order to propose effective therapeutic measures and to develop further insights into white matter response to disease in general. We plan to maintain a breeding colony of dogs to produce GLD offspring for experimental investigations. To clarify the role of cells that produce myelin in GLD, autoradiographic and morphometric techniques will be employed to detect cellular reactions at different stages of the pathologic process. Morphometry will be utilized to ascertain the extent of myelin normality prior to lesion development in GLD and normal control dogs. Having identified white matter regions and individual dogs that are resistant vs. susceetible in regard to rate of lesion development, by means of quantifying lesion distribution, morphologic and biochemical features that are correlated with susceptibility are being southt to gain insight into factors affecting the pathologic process. Isoenzymatic differences in dog and man will be contrasted to gain insight into enzymatic organization and the nature of the deficient enzymatic activity in the two species.